This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cardiovascular disease-CVD is the leading cause of mortality in the United States of America and hypertension is an important cardiovascular risk factor. It is also a risk factor for stroke, heart attack, renal failure and heart failure. Beta-blockers along with diuretics are among the recommended first-line agents for the treatment of hypertension. Data from various studies indicate that the risk of developing diabetes in hypertensive patients is related to the antihypertensive drug strategy. Type 2 diabetes comprises ~ 90% of new cases of diabetes and occurs in 60% of hypertensive patients. Beta-blockers and diuretics have been used for the treatment of hypertension for decades and have been shown to decrease cardiovascular morbidity and mortality rates in patients with essential hypertension. One of the arguments against the primary use of beta-blockers has been the concern about adverse metabolic effects on the lipid profile and on insulin sensitivity. Another side effect is the propensity of beta-blockers to cause weight gain. Obesity is now well recognized as an important predictor of overall mortality. Increased body weight is a clinical problem in the vast majority of hypertensive patients and almost all type 2 diabetic hypertensive patients. Although, various reports indicate low doses of diuretics to be free from negative effects on the lipid profile and insulin sensitivity;no such studies are reported for the beta-blockers. Through this study we will determine concentration response relationship between the occurrence of metabolic effects and beta-blocker systemic plasma concentrations.